A number of examples of complex bioactive compounds which exhibit cytotoxic, ichthyotoxic, or other biological activity have recently been isolated from various marine invertebrates (D'Auria, M. V., L. Minale, R. Riccio [1993]Chem. Rev. 93:1839). These bioactive compounds include certain secosteroids and pseudopterosins isolated from species of coral. Other useful compounds have also been isolated from marine organisms such as bacteria, bryozoans, sea squirts, sponges, or algae.
Secosteroids are a group of sterols structurally characterized by the absence of a bond in the nucleus. A group of three 9(11)-secosterols (formulae 1-3 in FIG. 1), isolated from marine organisms belonging to the genus Pseudopterogorgia, have been shown to be responsible for the chemical defense of the organism. For example, it has been demonstrated that secosteroids afford an efficient fish-feeding deterrent for the source gorgonian. Further, it has recently been demonstrated that certain 9(11)-secosterols (e.g., formula 1) exhibit inhibitory activity against protein kinase C and potent antiproliferative and anti-inflammatory activity (He, H., P. Kulanthaivel, B. J. Baker, K. Kalter, J. Darges, D. Cofield, L. Wolff [1995] Tetrahedron 51:51). There can therefore be considerable utility for these sterols in the pharmaceutical industry.
Another promising class of compounds that can be extracted from the marine soft coral of the genus Pseudopterogorgia is the pseudopterosins. Polar-lipid metabolites extracted from Pseudopterogorgia spp. have been shown to have analgesic, antimicrobial, anti-inflammatory, or cytotoxic activity. The pseudopterosins are non-steroidal terpenoid compounds having glycosidic (pentose) side chains. Look, et al. (1986) Proc. Nat'l. Acad. Sci. 83:6238-6240; Look (1986) J. Org. Chem. 51:5140-5145. Presently, twelve derivatives of the pseudopterosins (PsA-PsL) have been identified, each having a tricyclic ditripene structure and differing in their sugar side chain. Rousis (1990) J. Org. Chem. 55:4916-4922. Certain of these pseudopterosin compounds or their derivatives, including methods of treatment using the compounds or derivatives, have been described in U.S. Pat. Nos. 4,745,104, 4,849,410, 5,597,808, and 5,624,911, which are hereby incorporated by reference. Preferably, the pseudopterosin compounds are obtained from coral in the family Gorgoniidae, namely, Pseudopterogorgia elisabethae.
As with the vast majority of marine-derived bioactive agents, 9(11)-secosteroids and pseudopterosins are sufficiently complex that a completely synthetic approach to their production is an expensive and time-consuming undertaking. For example, the current synthetic method for producing the 9(11)-secosteroid 4 (FIG. 1) from 7-dehydrocholesterol acetate involves a seven-step procedure requiring numerous HPLC purifications and an overall yield of ca. 4.times.10.sup.-3 % (Adinolfi, R., A. Miglinolo, V. Piccialli, D. Sica [1994] J. Nat. Prod. 57:1220).
Besides synthetic procedures, compounds in the secosteroid class of steroids and non-steroidal class of pseudopterosins are generally collected from biomass, i.e., harvesting of source organisms for extraction therefrom. In the procedure involving collection from biomass, the pure compound, e.g. a steroid is obtained from a crude extract of the source organism by tedious chromatographic methods. A disadvantage of the biomass collection/purification procedure is that large quantities of organisms are required and are often obtained from sensitive marine habitats. Also, only the naturally-occurring compounds will be obtained. Therefore, there is a need in the pharmaceutical industry to produce secosterol or pseudopterosin compounds efficiently, inexpensively, and without causing undue stress or harm to the ecosystems or habitats of organisms that naturally produce these compounds.